Targeting the myofibroblast : new strategies in managing equine corneal fibrosis

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Corneal disease is a common cause of blindness in horses as a result of various causes including traumatic, autoimmune, neoplastic, or infectious disease. Although successful treatment of these underlying diseases may salvage the globe, the resulting corneal fibrosis from these pathologic processes can lead to significant vision loss. The objective of this research was to evaluate several potential therapies, nanoparticle gene therapy and a histone deacetylase inhibitor, for inhibiting the differentiation of equine corneal fibroblasts into myofibroblasts in vitro. This differentiaion of fibroblast to myofibroblast has been determined to be the major event responsible for corneal fibrosis, and is initiated by the presence of transforming growth factor beta. Our results indicate that polyethylenimine nanoparticle therapy is safe and effective and when delivering decorin, a natural antagonist of transforming growth factor beta, fibrosis is significantly inhibited in vitro. Additionally the histone deacytelase inhibitor suberoylanilide hydroxamic acid is an effective inhibitor of equine corneal fibrosis in vitro.